Sunitha Bachawal PhD, Presenter: Nothing to Disclose

Ferdinand Knieling, Abstract Co-Author: Nothing to Disclose

Amelie Margarete Lutz MD, Abstract Co-Author: Nothing to Disclose

Lu Tian, Abstract Co-Author: Nothing to Disclose

Juergen Karl Willmann MD, Abstract Co-Author: Research Consultant, Bracco Group Research Grant, Siemens AG Research Grant, Bracco Group

CD276 has been shown to be differentially expressed in various cancers including human breast cancer. Our goal was to compare the potential of ultrasound (US) molecular imaging using microbubbles (MB) targeted to CD276 with vascular endothelial growth factor receptor type2 (VEGFR2)-targeted MB for assessment of breast tissue progression to early breast cancer in transgenic mice (FVB/N Tg (MMTV/ PyMT634Mul).

A transgenic mouse model of breast cancer (FVB/N-Tg(MMTV-PyMT634Mul)) was used in this study. The progression of breast tissue from normal to invasive cancer was examined using US molecular imaging (Vevo2100, Visualsonics) with VEGFR2- and CD276- targeted MB in 160 mammary glands. Ex vivo expression levels of VEGFR2 and CD276 were examined using immunofluorescence staining followed by confocal microscopy.

There was a significant (p<0.001) increase of in vivo imaging signal of VEGFR2 and CD276-targeted US imaging when breast tissue progressed from normal (5.6 ± 0.95, 4.5 ± 0.7 a.u. respectively) to breast cancer (98.8 ± 8.78, 51.9 ± 5.3 a.u. respectively) in transgenic mice. At a sensitivity level of 85%, VEGFR2- and CD276-targeted US imaging can differentiate benign (normal+hyperplasia) from malignant entities (DCIS+Invasive) with specificities of 86% and 93%, respectively. Both VEGFR2-targeted (AUC of 91.2) and CD276-targeted (AUC of 90.9) US imaging allowed the differentiation of benign from malignant diseases with high accuracies. Diagnostic accuracy could further been improved (AUC of 95.1) when the US molecular imaging information from both markers was utilized for differentiation. Immunofluorescence confirmed VEGFR2 and CD276 expression on vascular endothelial cells.

Combined VEGFR2- and CD276- targeted molecular imaging information can further improve accuracy of US for in vivo assessment of breast tissue progression from normal to breast cancer in this transgenic mouse model

US molecular imaging of tumor angiogenesis using tumor specific endothelial markers in breast cancer may help improve accuracy of US in breast cancer detection in future clinical trials.

Bachawal, S, Knieling, F, Lutz, A, Tian, L, Willmann, J, Breast Cancer Detection with CD276-targeted Ultrasound Imaging.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13024528.html